S233: AXICABTAGENE CILOLEUCEL AS SECOND-LINE THERAPY FOR LARGE B-CELL LYMPHOMA IN TRANSPLANT-INELIGIBLE PATIENTS: FINAL ANALYSIS OF ALYCANTE, A PHASE 2 LYSA STUDY
Authors: Roch Houot, Emmanuel Bachy, Guillaume Cartron, Francois-Xavier Gros, Franck Morschhauser, Lucie Oberic, Thomas Gastinne, Pierre Feugier, Rémy Duléry, Catherine Thieblemont, Magalie Joris, Fabrice Jardin, Sylvain Choquet, Rene Olivier Casasnovas, Gabriel Brisou, Morgane Cheminant, Jacques Olivier Bay, Francisco Llamas, Cedric Menard, Karin Tarte, Marie-Helene Delfau-Larue, Emmanuel Itti, Clément Bailly, Yassine Al Tabaa, Camille Laurent, Francois Lemonnier
Journal: HemaSphere (2023)

Background: Patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) after first-line treatment who are unable to undergo high-dose chemotherapy (HDCT) and hematopoietic stem cell transplantation (HSCT) have poor outcomes and limited treatment options. In the ZUMA-7 study, Axicabtagene ciloleucel (axi-cel) demonstrated superior efficacy over standard of care (SOC) as second-line therapy in patients intended for transplant (Locke et al, NEJM 2022). Aims: The objective of the open-label, phase 2, ALYCANTE study (NCT04531046) was to evaluate the efficacy and safety of axi-cel in patients with R/R LBCL after 1 prior line of therapy not intended for HDCT/HSCT owing to age and/or comorbidities. Methods: Eligible patients were adults with R/R LBCL that was refractory to or had relapsed no more than 12 months after first-line chemoimmunotherapy and who were not deemed candidates for HDCT/HSCT based on physician's assessment and at least one of the following criteria: age ≥ 65 years; age ≥ 18 years and Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) score ≥3; or age ≥ 18 years and prior ASCT (as 1st line consolidation). The primary endpoint was the complete metabolic response (CMR) at 3 months from axi-cel infusion based on investigator assessment. The protocol was amended to allow an expansion of 22 additional patients for subgroup comparisons. Results: At the time of data cut-off, 40 patients (out of 62 infused patients) could be analyzed for the primary endpoint. Median on-study follow-up was 10 months. Median age was 68 years (range, 49-81; 45% ≥ 70 years), 30% had HCT-CI score ≥ 3, and 52.5% were refractory to first-line treatment. Overall, 37 patients (92.5%) received bridging chemotherapy (R-GEMOX). Twenty-seven patients (67.5%) were refractory to bridging therapy. The study met its primary endpoint with a CMR at 3 months of 70% versus 12% expected with SOC based on historical controls (Cazelles et al, Leukemia & Lymphoma 2021). Best OR and CR rates were 92.5% and 80%, respectively. Median PFS was 11 months and median OS was not reached. CRS occurred in 90% of patients, including 10% of grade 3-4. ICANS occurred in 55% of patients, including 20% of grade 3-4. Twelve patients (30%) were admitted to ICU. Seven patients died: 2 due to lymphoma and 5 due to fatal infections. Early evaluation of response showed that 64.7% (22/34) and 44.4% (16/36) of patients had a negative PET-CT and an undetectable ctDNA at day 14 post axi-cel infusion, respectively. Summary/Conclusion: In the ALYCANTE study, axi-cel as second-line treatment in patients with LBCL who were not deemed candidates for HDCT/HSCT appears feasible and induces high response rates. The final analysis with 22 additional patients (N=62 vs 40 patients at current cut-off) and a longer follow-up will be presented at the meeting, including subgroup analysis. Keywords: CAR-T, Diffuse large B cell lymphoma, Elderly